Presence Of Neurofibromatosis Research Articles

NF1 Gene Inactivation Acts as Tumor Driver in RET/RAS Negative Medullary Thyroid Carcinomas.

20% of sporadic MTC has no RET/RAS somatic alterations or other known gene alterations. Aim of this study was to investigate RET/RAS negative MTC for the presence of NF1 alterations. we studied 18 sporadic RET/RAS negative MTC cases: Next generation sequencing of tumoral and blood DNA was performed using a custom panel including the entire coding region of the NF1 gene. The effect of NF1 alterations on the transcripts were characterized by RT-PCR and the loss of heterozygosity of the other NF1 allele was investigated with Multiplex Ligation-dependent Probe Amplification. Two cases showed bi-allelic inactivation of NF1 with a prevalence of about 11% of RET/RAS negative cases. In a patient affected by neurofibromatosis there was a somatic intronic point mutation determining the transcript alteration in one allele and a germline loss of heterozygosity (LOH) in the other. In the other case described both the point mutation and the LOH were somatic events; this latter finding shows, for the first time, a driver role of NF1 inactivation in MTC independent of RET/RAS alterations and the presence of neurofibromatosis. About 11% of our series of sporadic RET/RAS negative MTC harbor biallelic inactivation of NF1 suppressor gene also regardless neurofibromatosis status. According to our results, NF1 alterations should be searched in all RET/RAS negative MTC as possible driver. Moreover, this finding reduces the number of negative sporadic MTCs and may have important clinical implications in the management of these tumors.

Meningeomas Múltiples Intracraneales en ausencia de Neurofibromatosis. Reporte de caso y revisión de la literatura

Los Meningiomas Múltiples (MM) se definen como la aparición de por lo menos dos meningiomas separados espacialmente y que ocurren al mismo tiempo, o más de dos meningiomas que crecen secuencialmente desde dos regiones claramente diferentes, no necesariamente del mismo subtipo patológico, sin la presencia de Neurofibromatosis. Los MM fueron descritos por primera vez en 1889; pero serian Cushing y Eisenhardt en 1938, los primeros en acuñar el término Meningioma y definir el significado de los MM o Meningiomatosis. Es una patología con una baja incidencia, generalmente de comportamiento benigno y de una presentación clínica variada que depende de la localización del meningioma. Actualmente, no se cuenta con una clara descripción fisiopatologica de la enfermedad, sin embargo, se han descrito alteraciones a nivel celular que promuven una diseminación clonal en las meninges. Su abordaje se debe realizar de manera múltidisciplinaria, descartando principalmente alteraciones de tipo genético. Adicionalmente, es necesario individualizar al paciente al momento de valorar el estado clínico y los hallazgos imageneologicos para determinar la necesidad de manejo quirurgico. A continuación se describe el caso de una paciente femenina de 48 años de edad atendida en el Hospital Universitario Mayor, con antecedente de resección de meningioma hace 10 años en región ponto cerebelosa y hace 2 años resección de meningioma en región frontal, a quien se le documentan mediante resonancia magnetica MM intracraneales, con estudio para neurofibromatosis negativo.

Management of pediatric CNS meningiomas: CCHE-57357 experience in 39 cases.

Our aim is to present our experience in the management of pediatric meningiomas in the largest referral center in Egypt for pediatric tumors focusing on variables including clinical picture, anatomic location, histopathology, treatment strategies, and outcome together with their possible correlation to prognosis. We retrospectively reviewed the medical records of 39 pediatric patients who were treated for CNS meningiomas in Children's Cancer Hospital-Egypt (CCHE-57357) 2007-2017. The prevalence of pediatric meningioma was 1.42%. Four cases had type 2 neurofibromatosis (NFII). The mean age was 8.19years. The presence of NFII was associated with challenging multiple lesions, older age of presentation and poorer prognosis and functional outcome. Convexity was the commonest location. Gross total resection (GTR) was achieved in 28 cases, subtotal resection (STR) in 8 cases, and biopsy was decided in 3 patients. Histopathological examination revealed WHO grade I in 16 patients and higher grades in 23 patients (59%). The 5-year overall survival (OS) rate was 87.8% while the 5-years event-free survival (EFS) rate was 85.6%. Tumor location, histopathology, and clinical presentation were not statistically correlated to prognosis. Pediatric CNS meningiomas are uncommon pediatric tumors but of an aggressive clinical and pathological behaviors as compared to adult meningiomas. The presence of NFII is associated with a poorer prognosis and functional outcomes. Although being challenging, the maximum and safe surgical excision should be exercised even in recurrent cases in order to achieve the best outcome. Adjuvant radiotherapy provides good tumor control for inoperable residual atypical or anaplastic meningiomas.

Co-relation of MRI findings in Optic-Pathway Glioma with the Presence of Neurofibromatosis

Background:뀀ഀȠOptic nerve glioma (also known as optic pathway glioma) is the most common primary neoplasm of the optic nerve. The tumor can arise anywhere along the optic pathway from behind the globe to the occipital cortex. Optic pathway gliomas (OPGs) are associated with high rate of visual morbidity and mortality. Studies have shown no specific clinical histologic or neuro imaging features to differentiate aggressive from non- aggressive OPGs. Purpose: The biological behaviour of optic pathway glioma is unpredictable and it is not clear if specific anatomical patterns may be of use in prognosis of the OPGs. The prognosis is reportedly better in OPGs associated with neurofibromatosis (NF). The purpose of the study was to compare the MRI findings between patients with NF, with those without NF and to determine prognostic imaging signs if any. Material and Methods - MRI studies of 41 patients with OPG (21 with NF and 20 without NF) were reviewed at presentation and at follow up. Statistical bivariate analysis was used to compare the size and extension of tumor between patients with and those without NF. Results:뀀ഀȠOrbital component of the optic nerve was most commonly involved in patients with NF (65%) with optic chiasma being the most common site of involvement (90%) in the non NF group. Extension beyond the optic pathway at diagnosis was more frequent in the non-NF group. In patients with NF, the morphological appearance of the optic nerve was preserved with the tumor being of limited size as compared to the patients in the non-NF group. Statistically significant correlation between MRI features and growth pattern of glioma was absent. Conclusion: As per our study we found that more than half the NF patient's tumor size remained stable in contrast to less than 5% of the non-NF group. Although no statistical correlation was found between MRI imaging and the biological behaviour of the tumor, we can infer that NF OPG is a separate entity from non-NF OPG with different prognostic features requiring a customised approach as per the type.

Neurological outcomes and surgical complications in 221 spinal nerve sheath tumors.

OBJECTIVE Among all primary spinal neoplasms, approximately two-thirds are intradural extramedullary lesions; nerve sheath tumors, mainly neurofibromas and schwannomas, comprise approximately half of them. Given the rarity of these lesions, reports of surgical complications are limited. The aim of this study was to identify the rates of new or worsening neurological deficits and surgical complications associated with the resection of spinal nerve sheath tumors and the potential factors related to these outcomes. METHODS Patients were identified through a search of an institutional neuropathology database and a separate review of current procedural terminology (CPT) codes. Age, sex, clinical presentation, presence of neurofibromatosis (NF), tumor type, tumor location, extent of resection characterized as gross total or subtotal, use of intraoperative neuromonitoring, surgical complications, presence of neurological deficit, and clinical follow-up were recorded. RESULTS Two hundred twenty-one tumors in 199 patients with a mean age of 45 years were identified. Fifty-three tumors were neurofibromas; 163, schwannomas; and 5, malignant peripheral nerve sheath tumors (MPNSTs). There were 70 complications in 221 cases, a rate of 32%, which included 34 new or worsening sensory symptoms (15%), 12 new or worsening motor deficits (5%), 10 CSF leaks or pseudomeningoceles (4%), 11 wound infections (5%), 5 cases of spinal deformity (2%), and 6 others (2 spinal epidural hematomas, 1 nonoperative cranial subdural hematoma, 1 deep venous thrombosis, 1 case of urinary retention, and 1 recurrent laryngeal nerve injury). Complications were more common in cervical (36%) and lumbosacral (38%) tumors than in thoracic (18%) lesions (p = 0.021). Intradural and dumbbell lesions were associated with higher rates of CSF leakage, pseudomeningocele, and wound infection. Complications were present in 18 neurofibromas (34%), 50 schwannomas (31%), and 2 MPNSTs (40%); the differences in frequency were not significant (p = 0.834). Higher complication rates were observed in patients with NF than in patients without (38% vs 30%, p = 0.189), although rates were higher in NF Type 2 than in Type 1 (64% vs 31%). There was no difference in the use of intraoperative neuromonitoring when comparing cases with surgical complications and those without (67% vs 69%, p = 0.797). However, the use of neuromonitoring was associated with a significantly higher rate of gross-total resection (79% vs 66%, p = 0.022). CONCLUSIONS Resection is a safe and effective treatment for spinal nerve sheath tumors. Approximately 30% of patients developed a postoperative complication, most commonly new or worsening sensory deficits. This rate probably represents an inevitable complication of nerve sheath tumor surgery given the intimacy of these lesions with functional neural elements.

Association of tumor location, extent of resection, and neurofibromatosis status with clinical outcomes for 221 spinal nerve sheath tumors.

OBJECT Intradural extramedullary spine tumors represent two-thirds of all primary spine neoplasms. Approximately half of these are peripheral nerve sheath tumors, mainly neurofibromas and schwannomas. Given the rarity of this disease and, thus, the limited analyses of clinical outcomes, the authors examined the association of tumor location, extent of resection, and neurofibromatosis (NF) status with clinical outcomes. METHODS Patients were identified through a search of the University of California, San Francisco, neuropathology database and a separate review of current procedural terminology codes. Data recorded included patient age, patient sex, clinical presentation, presence of NF, tumor type, tumor location, extent of resection (gross-total resection [GTR] or subtotal resection [STR]), and clinical follow-up. RESULTS Of 221 tumors in 199 patients (mean age 45 years), 53 were neurofibromas, 163 were schwannomas, and 5 were malignant peripheral nerve sheath tumors. The most common presenting symptom was spinal pain (76%), followed by weakness (36%) and sensory abnormalities (34%). Mean symptom duration was 16 months. In terms of spinal location, neurofibromas were more common in the cervical spine (74% vs 27%, p < 0.001), and schwannomas were more common in the thoracic and lumbosacral spine (73% vs 26%, p < 0.001). Rates of GTR were lower for neurofibromas than schwannomas (51% vs 83%, p < 0.001), regardless of location. Rates of GTR were lower for cervical (54%) than thoracic (90%) and lumbosacral (86%) lesions (p < 0.001). NF was associated with lower rates of GTR among all tumors (43% vs 86%, p < 0.001). The mean follow-up time was 32 months. Recurrence/progression was more common for neurofibromas than schwannomas (17% vs 7%, p = 0.03), although the mean time to recurrence/progression did not differ according to tumor type (45 vs 53 months, p = 0.63). As expected, GTR was associated with lower recurrence rates (4% vs 22%, p < 0.001). According to multivariate analysis, cervical location (OR 0.239, 95% CI 0.110-0.520) and presence of NF (OR 0.166, 95% CI 0.054-0.507) were associated with lower rates of GTR. In a separate model, only GTR (OR 0.141, 95% CI 0.046-0.429) was associated with tumor recurrence. CONCLUSIONS Resection is an effective treatment for spinal nerve sheath tumors. Neurofibromas were found more commonly in the cervical spine than in other regions of the spine and were associated with higher rates of recurrence and lower rates of GTR than other tumor types, particularly in patients with NF Types 1 or 2. According to multivariate analysis, both cervical location and presence of NF were associated with lower rates of GTR. According to a second multivariate model, the only variable associated with tumor recurrence was extent of resection. Maximal safe resection remains ideal for these lesions; however, patients with cervical tumors or NF should be counseled about their increased risk for recurrence.

Meningiomas in children and adolescents: a meta-analysis of individual patient data

The epidemiological, prognostic, and therapeutic features of child and adolescent meningioma are poorly defined. Clinical knowledge has been drawn from small case series and extrapolation from adult studies. This study was done to pool and analyse the clinical evidence on child and adolescent meningioma. Searches of PubMed, Medline, and Embase identified 35 case series of child and adolescent meningioma completed over the past 21 years. Individual patient data were obtained from 30 studies via direct communication with investigators. Primary outcomes were relapse-free survival (RFS) and overall survival. Prognostic variables were extent of initial surgery, use of upfront radiotherapy, age, sex, presence of neurofibromatosis, tumour location, and tumour grade. RFS and overall survival were analysed using Kaplan-Meier survival curves and multivariable Cox regression models. From a total of 677 children and adolescents with meningioma, 518 were eligible for RFS analysis and 547 for overall survival analysis. Multivariable analysis showed that patients who underwent initial gross-total resection had better RFS (hazard ratio 0·16, 95% CI 0·10-0·25; p<0·0001) and overall survival (0·21, 0·11-0·39; p<0·0001) than those who had subtotal resection. No significant benefit was seen for upfront radiotherapy in terms of RFS (0·59, 0·30-1·16; p=0·128) or overall survival (1·10, 0·53-2·28; p=0·791). Patients with neurofibromatosis type 2 (NF2) had worse RFS than those without neurofibromatosis (2·36, 1·23-4·51; p=0·010). There was a significant change in overall survival with time between patients with NF2 compared with those without neurofibromatosis (1·45, 1·09-1·92; p=0·011); although overall survival was initially better for patients with NF2 than for those without neurofibromatosis, overall survival at 10 years was worse for patients with NF2. Patients with WHO grade III tumours had worse RFS than those with WHO grade I (3·90, 2·10-7·26; p<0·0001) and grade II tumours (2·49, 1·11-5·56; p=0·027). Extent of initial surgical resection is the strongest independent prognostic factor for child and adolescent meningioma. No benefit for upfront radiotherapy was noted. Hence, aggressive surgical management, to achieve gross-total resection, is the initial treatment of choice. In the event of a subtotal resection, repeat resection is recommended to achieve maximum extirpation. Close observation is warranted for patients who have a subtotal resection or who have WHO grade III tumours. Patients without neurofibromatosis should have a minimum 10-year follow-up, whereas patients with NF2 should be considered a special risk category, necessitating life-long follow-up. None.

Clinical Course and Prognosis of Trochlear Nerve Schwannomas

To delineate the disease course and prognosis of patients with mass lesions of the fourth nerve presumed to be schwannomas. Nonrandomized retrospective case series. Thirty-seven consecutive cases of presumed trochlear nerve schwannoma from 9 tertiary university neuro-ophthalmology centers. Cases were collected, and their clinical characteristics on presentation and follow-up are described. Inclusion criteria were brain magnetic resonance imaging (MRI) with a lesion suggestive of a schwannoma along the course of the fourth nerve. Exclusion criteria were other causes of fourth nerve palsy, such as congenital, traumatic or microvascular; normal (or lack of) initial brain MRI; lack of adequate clinical information; and disappearance of the lesion on subsequent follow-up brain MRI. Demographics of patients, presence of neurofibromatosis, symptoms on presentation, vertical deviation, lesion size (on presentation and follow-up), length of follow-up, and outcomes of treatment for lesions or diplopia. Seven patients were excluded and of the 30 patients included in our series, patients were predominantly male (77%) with a mean age of 51 years (range 9-102 years). In contrast with prior case reports, almost all of our cases had a fourth nerve palsy on presentation (29/30), often isolated. Mean follow-up was 3.1 years (range 0.2 months to 11.1 years). There was no significant difference between initial and follow-up lesion size (4.4 vs. 5 mm) for patients who did not receive treatment of lesions (P = 0.36). Only 3 patients underwent neurosurgical resection and an additional patient received gamma-knife radiotherapy. The majority of patients (24/30) did not pursue strabismus surgery for vertical diplopia. Patients with isolated fourth nerve palsy and small lesions of the fourth nerve have a good prognosis and should be followed with serial MRI scans without neurosurgical intervention unless they develop signs of brain stem compression. Most patients with diplopia and benign fourth nerve lesions typical of trochlear nerve schwannoma can adapt with either prism spectacles or no treatment at all, although strabismus surgery can be successful.

Malignant peripheral nerve sheath tumour of the paranasal sinuses and the anterior skull base

Malignant peripheral nerve sheath tumours (MPNSTs) are highly aggressive neoplasms with a marked propensity for local recurrence and metastatic spread. The management of MPNSTs continues to challenge pathologists and surgeons. As MPNSTs of the paranasal sinuses and the skull base are rare, prognostic factors and treatment modalities have not been consistently identified. We present a case of MPNST of the anterior skull base and provide an overview of all MPNSTs reported since 1970, in which the tumour location was the anterior skull base or the paranasal sinuses. Literature review revealed 33 well-documented cases of MPNSTs in this anatomic location. These cases were analysed with emphasis on age, gender, affected site, therapy, outcome, presence of neurofibromatosis, local recurrence and metastases. Despite multimodal therapy and advances in surgical techniques, the prognosis of MPNST located in the paranasal sinuses and the anterior skull base remains dismal. Outcome is mainly a function of local control by surgical resection. Adjuvant radiochemotherapy has shown no benefit. It may therefore be advisable to abstain from radiochemotherapy in order to improve chances for surgical intervention in case of recurrent disease. Close follow-up investigations are indispensable.

Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): Long-term results in 106 patients treated in a single institution

To assess the long-term outcome and toxicity of fractionated stereotactic radiotherapy for acoustic neuromas in 106 patients treated in a single institution. Between October 1989 and January 2004, fractionated stereotactic radiotherapy (FSRT) was performed in 106 patients with acoustic neuroma (AN). The median total dose applied was 57.6 Gy in median single fractions of 1.8 Gy in five fractions per week. The median irradiated tumor volume was 3.9 mL (range, 2.7-30.7 mL). The median follow-up time was 48.5 months (range, 3-172 months). Fractionated stereotactic radiotherapy was well tolerated in all patients. Actuarial local tumor control rates at 3- and 5- years after FSRT were 94.3% and 93%, respectively. Actuarial useful hearing preservation was 94% at 5 years. The presence of neurofibromatosis (NF-2) significantly adversely influenced hearing preservation in patients that presented with useful hearing at the initiation of RT (p = 0.00062). Actuarial hearing preservation without the diagnosis of NF-2 was 98%. In cases with NF-2, the hearing preservation rate was 64%. Cranial nerve toxicity other than hearing impairment was rare. The rate of radiation induced toxicity to the trigeminal and facial nerve was 3.4% and 2.3%, respectively. Fractionated stereotactic radiotherapy is safe and efficacious for the treatment of AN, with mild toxicity with regard to hearing loss and cranial nerve function. FSRT might be considered as an equieffective treatment modality compared to neurosurgery and therefore represents an interesting alternative therapy for patients with AN.

Pediatric neurofibrosarcoma

Background/Purpose: Neurofibrosarcoma is rare in children, and the natural history and prognostic factors are not well described. The authors present a 57-year review of their experience. Methods: The charts of children with neurofibrosarcoma were reviewed retrospectively. Statistical analysis was performed using the X2 and unpaired t tests. Results: From 1944 to 2001, 38 patients under the age of 21 were diagnosed with neurofibrosarcoma. Twenty-two were boys. The average age at diagnosis was 13.8 years (range, 3 to 19.9 years). Nineteen patients (50%) had neurofibromatosis. The tumor site was as follows: extremity, 19 patients; trunk, 9 patients; head and neck, 7 patients; and retroperitoneum, 3 patients. The average tumor size was 10 cm. The margins after resection were as follows: grossly positive, 9; microscopically positive, 5; negative, 21; and unknown, 3. Patients with positive margins had a 22% survival rate, whereas those with negative or unknown margins had a 34% survival rate. Thirty-two patients achieved a complete response, 2 a partial response, and 4 progressed while on therapy. Twenty-six patients relapsed after a complete response (11 local, 10 distant, 5 both). Of the 15 patients with a distant relapse, 73% (11) relapsed in the lung. Twelve (32%) patients survived with an average follow-up of 14 years (range, 0.3 to 28 years). Nine patients were treated with chemotherapy, 9 with radiation, and 9 with both chemotherapy and radiation. Outcome was not significantly affected by gender, presence of neurofibromatosis, site, margin, or use of adjuvant therapy. Conclusion: Neurofibrosarcoma remains a rare disease in children with insufficient contemporary numbers to assess efficacy of therapy. Prognosis remains poor with a high incidence of relapse, particularly in the lungs, suggesting that more aggressive therapies to control both local and distant relapses are needed. J Pediatr Surg 38:343-346. Copyright 2003, Elsevier Science (USA). All rights reserved.

Prognostic Significance of Type 1 Neurofibromatosis (von Recklinghausen Disease) in Childhood Optic Glioma

ALTHOUGH THE ASSOCIATION between optic glioma and neurofibromatosis is well recognized, few studies have systematically compared the outcomes of patients with optic gliomas and neurofibromatosis and patients with optic gliomas without neurofibromatosis. In the present study, patients with optic gliomas and Type 1 neurofibromatosis (NF-1) were compared with patients with optic gliomas without NF-1, with respect to survival, time to tumor progression, and tumor location. Forty-four patients with optic gliomas who were evaluated between 1949 and 1991 were studied retrospectively. Sixteen of 44 patients(36%) met the National Institutes of Health criteria for NF-1. The medical records of all patients were examined, and letters of inquiry were sent to every living patient to ascertain current health statuses. Death certificates were obtained to determine causes of death. Follow-up averaged 7.2 years (10.2 yr for patients with NF-1, 5.4 yr for patients without NF-1). The 5- and 10-year survival rates for patients with optic gliomas and NF-1 were 93 and 81%, respectively. For those patients with optic gliomas who did not have NF-1, 5- and 10-year survival rates were 83 and 76%, respectively. Seventeen patients experienced tumor progression (5 with NF-1, 12 without NF-1). A difference was observed in the mean time to tumor progression (first relapse) between the two groups (mean time with NF-1, 8.37 yr; without NF-1, 2.39 yr[P < 0.01]). However, no significant difference in overall survival, as evaluated by a log-rank test of the respective Kaplan-Meier survival curves, was observed between the two groups. A significant difference in distribution of tumor location between the group with NF-1 and the group without NF-1 was also noted (Fisher's exact test, P = 0.0338), although the number of patients evaluated in this series was too small to determine whether this difference in tumor location influenced relapse rate. We conclude that optic gliomas in patients with neurofibromatosis have a different distribution of location as opposed to those in patients without neurofibromatosis, and, for first relapse, the presence of neurofibromatosis is a significant favorable factor.

265 Radiation therapy in optic gliomas of childhood: Prognosis and long term sequela

Thirty-three children with the diagnosis of optic glioma were admitted to Department of Radiation Oncology in Ankara University Faculty of Medicine between 1973 and 1994. Twenty-two patients were female and 11 were male, with a female:male ratio of 2:1. Their ages ranged between 1 to 18 (mean:8.4, median:7). Six patients (18.2%) presented with neurofibromatosis. Twenty-nine patients (87.9%) had histopathological diagnosis of astrocytoma. Tumors were confined to the optic nerve in 5 patients (15.1%), confined to the chiasma in 6 patients (18.2%) and involved both the optic nerve and chiasma in 22 patients (66.7%). Subtotal resection of the tumor was perfunned in 20 patients (60.6%). Thirteen patients received irradiation as sole therapy. Two patients were irradiated for recurrent tumors. Mean follow-up was 158 months. Actuarial survival for 5 and 10 years were 91.9% and 77.9% respectively. Age, sex and subtotal resection did not appear to correlate with survival. Presence of neurofibromatosis reminded bad prognosis. One patient developed precocious puberty, two others developed panhypopituitarism and one posterior hypopituitarism. One patient was diagnosed as organic brain syndrome at the age of 30 and two patients had anxiety disorder. Radiotherapy proved to be an effective for tumors involving chiasma where surgery is not feasible. Long tenn follow-up would disclose either treatment or tumor induced sequela.

Optic glioma in children: Surveillance, resection, or irradiation?

Eighty-seven consecutive children with newly diagnosed optic glioma were managed at University of Toronto hospitals 1958–1990. Overall the 10-year survival, relapse-free survival and freedom from second relapse rates were 84%, 68% and 85%. Twenty-seven patients relapsed or progressed, of whom 40% were free of a second relapse 10 years after the first relapse. Fourteen patients had a second relapse. Thirteen are dead. None survived 5 years after second relapse. Patients with anteriorly located tumors (N = 35), which involved the optic nerve, or chiasm and optic nerves, fared better than those with posteriorly located tumors (N = 52) with spread beyond the chiasm, 10-year survival 95% versus 76%, ( p = .02), 10-year relapse-free survival 80% versus 59% ( p = .02), respectively. For posterior tumors primary irradiation was more effective than primary subtotal resection for prevention of subsequent relapse, 10-year relapse-free survival 75% versus 41% ( p = .02), but salvage therapy was, in part, successful and multivariate analysis of prognostic factors influencing survival for posterior tumors indicated that neither primary resection nor primary irradiation were significant factors. For first relapse, primary irradiation and the presence of neurofibromatosis were the significant favorable factors. Since 1977 and for posterior optic glioma subtotal resection or surveillance were used in 21/29 (72%) patients compared with 4/23 (17%) previously. Ten-year survival rates before and after 1977 were 78% and 67% and 10-year relapse-free survival 64% and 56%, respectively.

Treatment of children with neurogenic sarcoma. Experience at the Children's Hospital of Philadelphia, 1958-1984.

Twenty-four children aged 3 months to 18 years (median, 12 years) were treated for neurogenic sarcoma at the Children's Hospital of Philadelphia Cancer Research Center from 1958 through 1984. Sixteen patients had neurofibromatosis (NF). The tumors arose in an extremity or in the trunk (15 patients), the retroperitoneum-pelvis (6), or other sites (3). Twelve children underwent grossly complete excision of localized sarcoma; of them, five had no known residual tumor and seven had proven microscopic residual disease. Ten of the remaining 12 patients had grossly visible, residual localized disease, and two had lung metastases. After operation, nine were treated on a protocol with local radiation therapy (4000-6000 rad) plus vincristine, actinomycin D, and cyclophosphamide with or without Adriamycin (doxorubicin). The other 15 were treated variably. At 3 years, the proportion of tumor-free survivors was 9 of 24 (37.5%). The significant favorable factors were the initial surgical removal of all gross tumor (9 of 12 with tumor excision were tumor-free survivors at 3 years compared to none of 12 with gross residual sarcoma; P less than 0.01), and a tumor mitotic rate under one per high-power field. No significant correlation was found between tumor-free survival expectancy and age, race, sex, the presence of NF, the site and size of the primary tumor, or use of the chemoradiotherapy regimen. More effective treatment programs are needed for children with neurogenic sarcoma, especially for those with unresectable tumors.

Hypertension from isolated thoracic aortic coarctation associated with neurofibromatosis

A 14-year-old boy presented with hypertension and symptomatic cervical root neurofibromatosis. Isolated thoracic aortic coarctation and large collaterals adjacent to the cervical spine were identified. Surgical correction of the coarctation allowed safe excision of the neurofibroma and reversal of hypertension. Hypertension in the presence of neurofibromatosis requires evaluation of a number of correctable etiologies.

The architecture of optic nerve gliomas with and without neurofibromatosis.

A retrospective clinicopathologic study of 34 patients with optic nerve glioma disclosed two important architectural tumor forms: circumferential-perineural pattern featuring tumor eruption and proliferation in the subarachnoid space correlating with the presence of neurofibromatosis, and an expansile-intraneural pattern correlating with the absence of neurofibromatosis. The 18 patients with neurofibromatosis had a mean age of 4.9 years at presentation and tended to be younger than the 16 patients without neurfibromatosis (mean age, 12 years). Instead of "arachnoidal hyperplasia," electron microscopic studies in the electron microscopic studies in the circumferential-perineural pattern showed tumor astrocytes admixed with reactive meningothelial cells, fibroblasts, and collagen in distended subarachnoid space. Florid invasion of the leptomeninges (arachnoidal gliomatosis) exhibited by many optic nerve gliomas in neurofibromatosis suggests that they are true neoplasms rather than hamartomas, but their frequent location in the distal anterior visual pathway often confers a good clinical prognosis.